What is the recommended approach for an elderly patient currently taking pregabalin (anticonvulsant) 75 mg three times a day (tid) who is requesting a dose increase?

Pregabalin Dose Escalation in Elderly Patients

In an elderly patient currently on pregabalin 75 mg three times daily (225 mg/day) requesting a dose increase, you should increase to 100 mg three times daily (300 mg/day) and wait a minimum of 2-4 weeks at this dose before considering any further escalation. 1, 2

Current Dose Assessment

Your patient is currently taking 225 mg/day, which is above the typical starting dose of 150 mg/day but below the standard therapeutic target of 300 mg/day. 1, 2

• The FDA-approved dosing for neuropathic pain begins at 150 mg/day (50 mg three times daily or 75 mg twice daily), with escalation to 300 mg/day within 1 week based on efficacy and tolerability. 2
• The standard effective dose for most neuropathic pain conditions is 300 mg/day (100 mg three times daily or 150 mg twice daily), which provides the optimal benefit-to-risk ratio. 1, 3

Recommended Titration Strategy

Increase to 300 mg/day (100 mg three times daily) as the next step. 1, 2

• This represents the evidence-based therapeutic target dose where most patients achieve adequate pain relief. 1, 3
• In elderly patients specifically, use slower titration with careful monitoring for dizziness, somnolence, confusion, balance disorders, and fall risk. 1, 3
• Wait a full 2-4 weeks at 300 mg/day before declaring inadequate response, as pregabalin's full analgesic effect requires adequate time at therapeutic dose. 1, 3

Critical Decision Point: Beyond 300 mg/day

Reserve doses above 300 mg/day ONLY for patients who have ongoing pain after an adequate trial at 300 mg/day AND tolerate the medication well. 1, 2

• The maximum dose of 600 mg/day (200 mg three times daily) is not consistently more effective than 300 mg/day but causes significantly more adverse effects and higher treatment discontinuation rates. 1, 2, 4
• Higher doses (>300 mg/day) show dose-dependent increases in dizziness (23-46%), somnolence (15-25%), and peripheral edema (10%). 3, 4
• For elderly patients, the increased risk of falls, confusion, and sedation at higher doses makes 300 mg/day the preferred maximum in most cases. 3

Monitoring and Safety Considerations

Closely monitor for dose-dependent adverse effects during titration: 3, 4

• Dizziness and somnolence are the most common side effects and can be managed by slowing titration or reducing dose without discontinuing therapy. 4
• Elderly patients are particularly susceptible to falls and confusion, requiring extra vigilance. 3
• If intolerable side effects occur at 300 mg/day, consider "asymmetric dosing" with a larger evening dose (e.g., 75 mg morning, 75 mg afternoon, 150 mg evening) to minimize daytime sedation. 5

Renal Function Consideration

Verify renal function before dose escalation, as pregabalin is eliminated 98% unchanged by the kidneys. 2, 6

• Mandatory dose reduction is required for creatinine clearance <60 mL/min. 2
• For CrCl 30-60 mL/min: reduce total daily dose by approximately 50%. 3
• For CrCl 15-30 mL/min: reduce by 75%. 3
• For CrCl <15 mL/min: reduce by 85-90%. 3

Common Pitfall to Avoid

Do not routinely prescribe 600 mg/day as a standard dose. 3

• The evidence clearly demonstrates that 300 mg/day provides optimal benefit-to-risk ratio for most patients, with 600 mg/day reserved only for the subset with inadequate response at 300 mg/day who tolerate the medication well. 1, 3
• In elderly patients, the risk-benefit ratio at 600 mg/day is particularly unfavorable due to increased fall risk and cognitive side effects. 3

Discontinuation Protocol

If pregabalin ultimately needs to be discontinued, taper gradually over a minimum of 1 week to avoid withdrawal symptoms. 2